COQ9

Chr 16AR

coenzyme Q9

Also known as: C16orf49, COQ10D5

NCBI Gene: 57017ENSG00000088682UniProt: O75208

This locus represents a mitochondrial ubiquinone biosynthesis gene. The encoded protein is likely necessary for biosynthesis of coenzyme Q10, as mutations at this locus have been associated with autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency.[provided by RefSeq, Sep 2010]

Primary Disease Associations & Inheritance

Coenzyme Q10 deficiency, primary, 5MIM #614654
AR
386
ClinVar variants
46
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COQ9
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 159 VUS of 386 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.01LOEUF
pLI 0.000
Z-score 1.53
OE 0.61 (0.38–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.22Z-score
OE missense 1.05 (0.93–1.18)
183 obs / 174.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.38–1.01)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.93–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 11 / 18.0Missense obs/exp: 183 / 174.9Syn Z: 0.18

ClinVar Variant Classifications

386 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic8
VUS159
Likely Benign148
Benign18
Conflicting15
38
Pathogenic
8
Likely Pathogenic
159
VUS
148
Likely Benign
18
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
1
29
0
38
Likely Pathogenic
5
0
3
0
8
VUS
2
132
25
0
159
Likely Benign
0
7
62
79
148
Benign
0
1
16
1
18
Conflicting
—15
Total1514113580386

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COQ9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

COQ9-related coenzyme Q10 deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
COENZYME 9; COQ9
MIM #612837 · *

Coenzyme Q10 deficiency, primary, 5

MIM #614654

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COQ9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Homozygous COQ9 mutation: a new cause of potentially treatable hereditary spastic paraplegia.
Fontaine F et al.·Eur J Hum Genet
2025Case report
New variants expand the neurological phenotype of COQ7 deficiency.
Fabra MA et al.·J Inherit Metab Dis
2024
Two cases of neonatal hyperglycemia caused by a homozygous COQ9 stop-gain variant.
Donis R et al.·J Diabetes Investig
2025Case report
Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.
Danhauser K et al.·Eur J Hum Genet
2016Case report
Modelling the human coenzyme Q deficiency in Drosophila melanogaster.
Fernández-Ayala DJM et al.·Free Radic Biol Med
2025Functional
A family segregating lethal neonatal coenzyme Q(10) deficiency caused by mutations in COQ9.
Smith AC et al.·J Inherit Metab Dis
2018
Genetic bases and clinical manifestations of coenzyme Q10 (CoQ 10) deficiency.
Desbats MA et al.·J Inherit Metab Dis
2015Review
Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency.
García-Corzo L et al.·Hum Mol Genet
2013Functional
Safety assessment of coenzyme Q10 (CoQ10).
Hidaka T et al.·Biofactors
2008Review
Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10).
Horvath R·J Inherit Metab Dis
2012Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools